Neurotransmitter receptor plasticity in aging

Neurotransmitter receptor plasticity is an important part of the compensatory processes by which the central nervous system adapts to pathological insult, long-term exposure to drugs or neuronal loss with advanced age. Receptor plasticity can be manifest as changes in the number of receptors (i.e., up- or down-regulation), changes in expression of mRNA for discrete receptor proteins, or alterations in receptor coupling to signal transduction systems. Evidence exists for impaired plasticity of neurons in the aged brain, which results in decreased ability to adjust to changes in their environment. However, such data are highly dependent on the neurotransmitter examined, the stimulus for receptor regulation and the animal model chosen for study. For example, senescent rats show an age-related impairment of muscarinic receptor up- or down-regulation after long-term exposure to cholinergic drugs. Thus, young rats exposed to chronic (three weeks) intracerebroventricular infusions of methylatropine or oxotremorine exhibit compensatory changes in the density of muscarinic receptors in frontal cortex and hypothalamus. In contrast, 3H-QNB binding is unaltered in the same brain regions of identically treated senescent rats. Similar observations of impaired muscarinic receptor plasticity in senescent animals have been confirmed by other investigators. Age-related differences in coupling of brain muscarinic receptors to G-proteins and in muscarinic receptor-stimulated phosphoinositide hydrolysis have also been reported. Interestingly, neuropeptides such as neurotensin, cholecystokinin and VIP can potentiate carbachol-stimulated phosphoinositide hydrolysis in frontal cortex of both young and aged rats. This adds another level at which cholinergic neurotransmission may be modulated in senescent animals. Potential age-related differences in the effects of chronic drug treatments or experimental brain lesions on muscarinic receptor coupling to second messenger systems or on expression of mRNA for particular muscarinic receptors are currently unknown. Hence, it is possible that senescent animals may show additional deficiencies in plasticity of muscarinic receptor mediated signal transduction or expression of muscarinic receptors subtypes.     

Energy storage options for wireless sensors powered by aircraft specific thermoelectric energy harvester

This paper describes an approach for efficiently storing the harvested energy from a thermoelectric module for powering autonomous wireless sensor nodes in aircraft health monitoring applications. Thermoelectric devices are the preferred option due to the widespread availability of significant levels of energy from the temperature gradients or variations at the aircraft, such as the cabin, the engine compartment, the fuel tanks or the inner and outer frame of the fuselage. Batteries and supercapacitors are popular choices of storage device, but neither represents the ideal solution, with, supercapacitors possessing low energy densities while batteries have low power density. When using a battery-only solution for storage, the runtime of a typical sensor node is typically reduced by the battery’s relatively high internal impedance and thermal loss. Supercapacitors can overcome some of these problems, but generally do not provide sufficient long-term energy to allow aircraft health monitoring applications to be operated over an extended period. A hybrid energy storage solution can provide both energy and power density to a wireless sensor node simultaneously. Techniques such as acoustic–ultrasonic, acoustic-emission, strain and crack wire sensors require storage approaches that can provide immediate energy on demand, usually in short, high intensity bursts, and that can be sustained over long periods of time, storing up to 40–50 J of energy. This application requirement is considered as a significant constraint when working with battery-only and supercapacitor-only solutions. The hybrid system described here provides an alternate viable solution.     

Cloning of the late genes in the ergosterol biosynthetic pathway ofSaccharomyces cerevisiae—A review

Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents. Nine of the eleven genes in the portion of the pathway committed exclusively to ergosterol biosynthesis have been cloned, and their essentiality for aerobic growth has been determined. The first three genes;ERG9 (squalene synthase),ERG1 (squalene epoxidase), andERG7 (lanosterol synthase), have been cloned and found to be essential for aerobic viability since their absence would result in the cell being unable to synthesize a sterol molecule. The remaining eight genes encode enzymes which metabolize the first sterol, lanosterol, to ultimately form ergosterol. The two earliest genes,ERG11 (lanosterol demethylase) andERG24 (C-14 reductase), have been cloned and found to be essential for aerobic growth but are suppressed by mutations in the C-5 desaturase (ERG3) gene andfen1 andfen2 mutations, respectively. The remaining cloned genes,ERG6 (C-24 methylase),ERG2 (D8Æ7 isomerase),ERG3 (C-5 desaturase), andERG4 (C-24(28) reductase), have been found to be nonessential. The remaining genes not yet cloned are the C-4 demethylase and the C-22 desaturase (ERG5).     

Analysis of an efficient rule-based motion planning system for simulating human crowds

This paper proposes a rule-based motion planning system for agent-based crowd simulation, consisting of sets of rules for both collision avoidance and collision response. In order to avoid an oncoming collision, a set of rules for velocity sampling and evaluation is proposed, which aims to choose a velocity with an expected time to collision larger than a predefined threshold. In order to improve the efficiency over existing methods, the sampling procedure terminates upon finding an appropriate velocity. Moreover, the proposed motion planning system does not guarantee a collision-free movement. In case of collision, another set of rules is also defined to direct the agent to make a corresponding response. The experiment results show that the proposed approach can be applied in different scenarios, while making the simulation execution efficient.     

Radiopharmacology of inhaled 133Xe in skeletal sites containing deposits of Gaucher cells

Gaucher's disease is a lysosomal storage disease in which cells of the reticuloendothelial system accumulate the lipid glucocerebroside. It is characterized by slowly progressive visceral and osseous involvement. One of the latter manifestations includes lipid infiltration of bone marrow. We monitored the rate of inhaled 133Xe uptake and wash-out over diseased and normal metaphyseal and epiphyseal areas of the knee. Twenty-two patients (15 adults, 7 children) with various degrees of previously diagnosed Gaucher's disease were positioned supine under a gamma-camera interfaced to a computer system. All patients rebreathed 133Xe gas from a closed system for 10 min followed by 14 min of wash-out. Digitized images of the lung, liver, spleen, bony sites and soft tissue were obtained at 1 min intervals during the wash-in and wash-out phases. Counts for each ROI were normalized per 100 pixels and plotted as a function (time). Maximum uptake was also calculated by relating the counts/ROI/100 pixels to the 10 min integrated lung count during equilibrium (the administered "dose"). There was essentially no 133Xe uptake in liver and spleen involved with Gaucher's disease. Monophasic uptake and biphasic wash-out curves were observed in the limited investigative population. Skeletal Gaucher deposits released the 133Xe at a greater rate relative to soft tissue.     

Energy supplier obligations and white certificate schemes: Comparative analysis of experiences in the European Union

A number of Member States of the European Union (EU) have introduced market-based policy portfolios based on quantified energy savings obligations on energy distributors or suppliers, possibly coupled with certification of project-based energy savings (via white certificates), and the option to trade the certificates or obligations. The paper provides an up-to-date review and analysis of results to date of white certificate schemes in the EU.     

The Hermite radial basis function control volume method for multi-zones problems; A non-overlapping domain decomposition algorithm

In this paper a non-overlapping non-iterative multi-domain formulation for the control volume Hermite radial basis functions (CV-HRBF) method is proposed, where the local Hermitian RBF meshless collocation method is used to satisfy a physical matching condition at the sub-domain boundaries. In addition, the robustness of the Hermite interpolation is exploited even further to apply multiple flux continuities for those cases where more than two sub-domains converge in the same point. The algorithm is first validated in one-dimensional advection diffusion problems for which an analytical solution is known. Its accuracy is compared with a classic CV approach and a local radial basis function collocation method (LRBFCM). More general applications in two and three-dimensional domains are then considered. A heat transfer problem in strongly heterogeneous materials, and a groundwater flow problem in presence of geological layers characterised by different hydraulic conductivity, are taken as engineering applications to test the capabilities of the CV-HRBF method to handle multi-zone problems. Finally, the transport of a single species is simulated in a one-dimensional channel consisting of two adjacent zones that feature different Peclet numbers.     

Modeling of an Unbonded CFRP Strap Shear Retrofitting System for Reinforced Concrete Beams

A retrofitting technique has been developed that uses carbon fiber-reinforced polymer (CFRP) straps to increase the shear capacity of reinforced concrete beams. The vertical straps are not bonded to the beam but are instead anchored against the beam, which makes this technique potentially more effective than bonded FRP retrofitting techniques. However, it also means that models for bonded FRPs are not appropriate for use with the straps. Instead, a model based on a shear friction approach has been developed where the strain in the straps is calculated based on a term that accounts for the effects of prestress and additional strain in the strap due to shear crack opening. The model can either consider the shear reinforcement to be smeared along the length of the beam or discrete elements. The “smeared” model was checked against an experimental database consisting of rectangular, T-, and deep beams, both in terms of predicted capacity and predicted strain in the straps. Overall the smeared model predicted the capacity of the specimens and, with some adjustments, the strains quite accurately. There were, however, cases when it was more appropriate to use the “discrete” model such as when the transverse reinforcement ratio was low or when the transverse reinforcement spacing was high. Further experimental data are required to fully validate the models and to determine appropriate limits on the use of the smeared model and the discrete model. However, the initial results are promising.